From the Guidelines
Elevated Liver Function Tests (LFTs) are a biochemical indication of hepatobiliary insult, rather than a direct measurement of liver function, and can be caused by various factors such as hepatocellular damage, cholestasis, or bile flow obstruction, as noted in the 2023 study by the Journal of the American College of Radiology 1. When evaluating elevated LFTs, it is essential to consider the different types of liver enzymes and their respective elevations.
- Hepatocellular predominant abnormal LFTs are reflected as an increase in aminotransferases, specifically alanine transaminase (ALT) and aspartate transaminase (AST), with ALT being more specific for liver injury due to its low concentrations in skeletal muscle and kidney 1.
- The severity of abnormal aminotransferase can be classified as mild, moderate, or severe, with moderate and severe being discussed collectively due to significant clinical overlap between these two categories 1. Some key points to consider when evaluating elevated LFTs include:
- Normal ALT levels are 29 to 33 IU/L (0.48-0.55 mkat/L) in men and 19 to 25 IU/L (0.32-0.42 mkat/L) in women, as reported in the 2023 study 1.
- Pathologically increased levels of alkaline phosphatase (ALP) may occur in cholestatic liver disease, which can show elevated ALP with or without elevated bilirubin, and if abnormal ALP levels are seen without impairment of other liver enzymes, the etiology is suspected to be cholestatic in origin 1. It is crucial to promptly evaluate and manage elevated LFTs to prevent further liver damage and promote healing, and this can be achieved by stopping potentially hepatotoxic medications or substances, undergoing further testing to determine the cause, avoiding alcohol consumption, and following a liver-friendly diet, as well as considering supplements under medical supervision and monitoring LFTs regularly 1.
From the Research
Definition of Elevated Liver Function Tests (LFTs)
Elevated Liver Function Tests (LFTs) refer to abnormal results from a group of tests used to assess liver function and detect liver disease. These tests include various biochemical markers, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin, among others 2.
Causes of Elevated LFTs
The causes of elevated LFTs can be diverse and include:
- Acute hepatitis, acute liver failure, and drug-induced liver injury (DILI) 3
- Exacerbations of pre-existing liver diseases, such as chronic hepatitis B and C, autoimmune hepatitis, non-alcoholic steatohepatitis, and hemochromatosis 4
- Secondary liver injury during critical diseases, such as sepsis, right heart failure, or cardiogenic shock, resulting in ischemic or hypoxic hepatitis 3
- Complications of ICU treatment measures, like drug-related hepatotoxicity, secondary sclerosing cholangitis, or related to parenteral nutrition 3
Evaluation of Elevated LFTs
The evaluation of elevated LFTs typically involves:
- Repeating the test to confirm the result 4
- Differentiating between a predominant "necrotic pattern" of liver chemistry (elevation of ALT or AST) and a predominant "cholestatic pattern" (elevation of gamma-glutamyl transferase (g-GT) and alkaline phosphatase) 4
- Non-invasive serologic tests to exclude hepatic diseases, such as chronic hepatitis B and C, autoimmune hepatitis, and non-alcoholic steatohepatitis 4
- Ultrasound, mini-laparoscopy, and liver biopsy to establish a final diagnosis if non-invasive tests remain inconclusive 4
Clinical Significance of Elevated LFTs
Elevated LFTs can be associated with increased mortality, particularly in critically ill patients 3. The presence of abnormal LFTs may be the first indication of subclinical liver disease and can guide further diagnostic evaluation 2. The pattern of liver test abnormalities can suggest the underlying cause of liver disease, such as hepatitis, biliary obstructions, or infiltrative liver disease 2.